Small conformational changes occurring in the discrete steps of the bacteriorhodopsin (bR) photocycle will be characterized by three- dimensional difference Fourier maps, using electron diffraction data. The first objective is to characterize the structural differences between the M-state intermediate and the light-adapted, bR568 ("resting") state. Further work on other intermediates in the photocycle will begin by establishing techniques that can trap different, specific intermediates at high occupancy, in a form suitable for electron diffraction studies. in related work, electron diffraction will be used to test a recently proposed hypothesis that bR adopts two distinct structural conformations, one when it binds an all trans configuration of retinal and the other when it binds 13-cis retinal. As a result of these structural studies, we hope to understand the precise molecular mechanism of active ion transport, as it occurs in bacteriorhodopsin. The new insights so gained may have broader relevance to active ion transport and bioenergetics, generally.